A5078346719- Amyotrophic Lateral Sclerosis Research
- Alzheimer's disease research and treatments
- Parkinson's Disease Mechanisms and Treatments
- Trace Elements in Health
- Pregnancy and Medication Impact
- Peptidase Inhibition and Analysis
- Pharmacological Effects and Toxicity Studies
- Neurogenetic and Muscular Disorders Research
- Multiple Myeloma Research and Treatments
- Neuroscience and Neuropharmacology Research
- Muscle Physiology and Disorders
- Analytical chemistry methods development
- Berberine and alkaloids research
- Pregnancy and preeclampsia studies
- X-ray Diffraction in Crystallography
- Radioactive element chemistry and processing
- Neuroinflammation and Neurodegeneration Mechanisms
- Cholinesterase and Neurodegenerative Diseases
- Mass Spectrometry Techniques and Applications
- Crystallization and Solubility Studies
- Alkaloids: synthesis and pharmacology
- Signaling Pathways in Disease
- Plant-based Medicinal Research
- Iron Metabolism and Disorders
- Hemoglobinopathies and Related Disorders
The University of Melbourne
2017-2025
Florey Institute of Neuroscience and Mental Health
2018-2024
Victoria College
2018
University of Helsinki
2009-2016
Biocenter Finland
2009
Abstract The copper compound Cu II (atsm) has progressed to phase 2/3 testing for treatment of the neurodegenerative disease amyotrophic lateral sclerosis (ALS). is neuroprotective in mutant SOD1 mouse models ALS where its activity ascribed part improving availability essential copper. However, mutations cause only ~ 2% cases and therapeutic relevance sporadic unresolved. Herein we assessed spinal cord tissue from human copper-related changes. We found that when compared control natural...
Abstract Aberrant self-assembly and toxicity of wild-type mutant superoxide dismutase 1 (SOD1) has been widely examined in silico, vitro transgenic animal models amyotrophic lateral sclerosis. Detailed examination the protein disease-affected tissues from sclerosis patients, however, remains scarce. We used histological, biochemical analytical techniques to profile alterations SOD1 deposition, subcellular localization, maturation post-translational modification post-mortem spinal cord cases...
Abstract Background Ferroptosis is a form of regulated cell death characterised by lipid peroxidation as the terminal endpoint and requirement for iron. Although it protects against cancer infection, ferroptosis also implicated in causing neuronal degenerative diseases central nervous system (CNS). The precise role yet to be fully resolved. Methods To elucidate we utilised co-culture conditioned medium transfer experiments involving microglia, astrocytes neurones. We ratified clinical...
Abstract Demyelination within the central nervous system (CNS) is a significant feature of debilitating neurological diseases such as multiple sclerosis and administering copper-selective chelatorcuprizone to mice widely used model demyelination in vivo. Conspicuous corpus callosum generally attributed cuprizone's ability restrict copper availability this vulnerable brain region. However, small number studies that have assessed tissue from cuprizone-treated produced seemingly conflicting...
The global incidence of metabolic and age-related diseases, including type 2 diabetes Alzheimer's disease, is on the rise. In addition to traditional pharmacotherapy, drug candidates from complementary alternative medicine are actively being pursued for further development. Berberine, a nutraceutical traditionally used as an antibiotic, has recently been proposed act multi-target protective agent against diabetes, dyslipidemias, ischemic brain injury neurodegenerative such Parkinson's...
Abstract Atypical wild-type superoxide dismutase 1 (SOD1) protein misfolding and deposition occurs specifically within the degenerating substantia nigra pars compacta (SNc) in Parkinson disease. Mechanisms driving formation of this pathology relationship with SNc dopamine neuron health are yet to be fully understood. We applied proteomic mass spectrometry synchrotron-based biometal quantification post-mortem brain tissues from disease patients age-matched controls uncover key factors...
Amyloid-β plaques, consisting of aggregated amyloid-β peptides, are one the pathological hallmarks Alzheimer's disease. Copper complexes formed using positron-emitting copper radionuclides that cross blood-brain barrier and bind to specific molecular targets offer possibility noninvasive diagnostic imaging positron emission tomography. New thiosemicarbazone-pyridylhydrazone based ligands incorporate pyridyl-benzofuran functional groups designed plaques have been synthesized. The form stable...
Oxidative stress is implicated in the insidious loss of muscle mass and strength that occurs with age. However, few studies have investigated role iron, which elevated during ageing, age-related wasting blunted repair after injury. We hypothesized iron accumulation leads to membrane lipid peroxidation, wasting, increased susceptibility injury, impaired regeneration.To examine atrophy, we compared skeletal muscles 3-month-old 22- 24-month-old 129SvEv FVBM mice. assessed distribution total...
Abnormal phosphorylation and aggregation of the microtubule-associated protein Tau are hallmarks various neurodegenerative diseases, such as Alzheimer disease. Molecular mechanisms that regulate complex currently incompletely understood. We have developed a novel live cell reporter system based on protein-fragment complementation assay to study dynamic changes in status. In this assay, fusion proteins Pin1 (peptidyl-prolyl cis-trans-isomerase 1) carrying complementary fragments luciferase...
Metals are found ubiquitously throughout an organism, with their biological role dictated by both chemical reactivity and abundance within a specific anatomical region.Within the brain, metals have highly compartmentalized distribution, depending on primary function they play central nervous system.Imaging spatial distribution of has provided unique insight into biochemical architecture allowing direct correlation between neuroanatomical regions known regard to metal-dependent processes.In...
Beta-thalassaemia is an inherited blood disorder characterised by ineffective erythropoiesis and anaemia. Consequently, hepcidin expression reduced resulting in increased iron absorption primary overload. Hepcidin under the negative control of transmembrane serine protease 6 (TMPRSS6) via cleavage haemojuvelin (HJV), a co-receptor for bone morphogenetic protein (BMP)-mothers against decapentaplegic homologue (SMAD) signalling pathway. Considering central role TMPRSS6/HJV/hepcidin axis...
Background: Neuroinflammation and biometal dyshomeostasis are key pathological features of several neurodegenerative diseases, including Alzheimer's disease (AD). Inflammation biometals linked at the molecular level through regulation metal buffering proteins such as metallothioneins. Even though connections between metals inflammation have been demonstrated, little information exists on effect copper modulation brain inflammation. Methods: We demonstrate immunomodulatory potential...
<ns4:p><ns4:bold>Background:</ns4:bold>Paracetamol (acetaminophen) is widely used in pregnancy and generally regarded as “safe” by regulatory authorities.</ns4:p><ns4:p><ns4:bold>Methods:</ns4:bold>Clinically relevant doses of paracetamol were administered intraperitoneally to pregnant rats twice daily from embryonic day E15 19 (chronic) or a single dose at E19 (acute). Control samples un-treated age-matched animals. At E19, anaesthetised, final dose, uteruses opened fetuses exposed for...
Tumours are abnormal growths of cells that reproduce by redirecting essential nutrients and resources from surrounding tissue. Changes to cell metabolism trigger the growth tumours reflected in subtle differences between chemical composition healthy malignant cells. We used LA-ICP-MS imaging investigate whether these can be spatially identify support detection primary colorectal anatomical pathology. First, we generated quantitative images three surgical resections with case-matched normal...
Abstract Aims To describe the clinical characteristics and medication purchases of insulin‐treated adults in Finland at index (January 1, 2012 or first insulin purchase) December 31, 2019. Additionally, to basal (BI) treatment patterns associated changes hemoglobin A1c (HbA1c) values. Materials Methods In this descriptive study using nationwide registries, we included with least two reimbursed within 12 months purchase between January We formed four groups: type 1 diabetes (T1D) 2...
Abstract Disrupted copper availability in the central nervous system (CNS) is implicated as a significant feature of neurodegenerative disease amyotrophic lateral sclerosis (ALS). Solute carrier family 31 member 1 (Slc31a1; Ctr1) governs uptake mammalian cells and mutations affecting Slc31a1 are associated with severe neurological abnormalities. Here, we examined impact decreased CNS caused by ubiquitous heterozygosity for functional on spinal cord motor neurons Slc31a1+/− mice. Congruent...
Mutations to the copper-dependent enzyme Cu/Zn-superoxide dismutase (SOD1) cause amyotrophic lateral sclerosis (ALS) in humans, and transgenic overexpression of mutant SOD1 represents a robust murine model disease. We have previously shown that copper-containing compound CuII(atsm) phenotypically improves mice delivers copper copper-deficient CNS restore its physiological function. is now clinical trials for treatment ALS. In this study, we demonstrate cuproenzyme dysfunction extends beyond...
<ns4:p><ns4:bold>Background:</ns4:bold>Paracetamol (acetaminophen) is widely used in pregnancy and generally regarded as “safe” by regulatory authorities.</ns4:p><ns4:p><ns4:bold>Methods:</ns4:bold>Clinically relevant doses of paracetamol were administered intraperitoneally to pregnant rats twice daily from embryonic day E15 19 (chronic) or a single dose at E19 (acute). Control samples un-treated age-matched animals. At E19, anaesthetised, final dose, uteruses opened fetuses exposed for...
Dysregulation of brain iron metabolism is one the pathological features aging and Alzheimer’s disease (AD), a neurodegenerative characterized by progressive memory loss cognitive impairment. While physical inactivity risk factors for AD regular exercise improves function reduces pathology associated with AD, underlying mechanisms remain unclear. The purpose study to explore effect on modulation homeostasis in periphery 5xFAD mouse model AD. By using inductively coupled plasma mass...
Oxidative stress is implicated in the pathophysiology of Duchenne muscular dystrophy (DMD, caused by mutations dystrophin gene), which most common and severe dystrophies. To our knowledge, distribution iron, an important modulator oxidative stress, has not been assessed DMD. We tested hypotheses that iron accumulation occurs mouse models DMD modulation through diet or chelation could modify disease severity.We total elemental using LA-ICP-MS on skeletal muscle cross-sections 8-week-old Bl10...